November 2008

29 November 2008

Researchers have uncovered what may be a universal cause of aging,
one that applies to both single cell organisms such as yeast and
multicellular organisms, including mammals. This is the first time that
such an evolutionarily conserved aging mechanism has been identified
between such diverse organisms.

The mechanism probably dates back more than one billion years. The
study shows how DNA damage eventually leads to a breakdown in the
cell's ability to properly regulate which genes are switched on and off
in particular settings.

Like our current financial crisis, the aging process might also be a product excessive deregulation.

Researchers have discovered that DNA damage decreases a cell's
ability to regulate which genes are turned on and off in particular
settings. This mechanism, which applies both to fungus and to us, might
represent a universal culprit for aging.

"This is the first potentially fundamental, root cause of aging that
we've found," says Harvard Medical School professor of pathology David
Sinclair. "There may very well be others, but our finding that aging in
a simple yeast cell is directly relevant to aging in mammals comes as a
surprise."

These findings appear in the November 28 issue of the journal Cell.

...

"It is remarkable that an aging mechanism found in yeast a decade
ago, in which sirtuins redistribute with damage or aging, is also
applicable to mammals," says Leonard Guarente, Novartis Professor of
Biology at MIT, who is not an author on the paper. "This should lead to
new approaches to protect cells against the ravages of aging by finding
drugs that can stabilize this redistribution of sirtuins over time."

Both Sinclair and Oberdoerffer agree with Guarente's sentiment that these findings may have therapeutic relevance.

"According to this specific mechanism, while DNA damage exacerbates
aging, the actual cause is not the DNA damage itself but the lack of
gene regulation that results," says Oberdoerffer. "Lots of research has
shown that this particular process of regulating gene activity,
otherwise known as epigenetics, can be reversed—unlike actual mutations
in DNA. We see here, through a proof-of-principal demonstration, that
elements of aging can be reversed."

19 November 2008

A Monash University scientist has discovered key appetite control
cells in the human brain degenerate over time, causing increased hunger
and potentially weight-gain as we grow older.

...

Dr Andrews found that appetite-suppressing cells are attacked by
free radicals after eating and said the degeneration is more
significant following meals rich in carbohydrates and sugars.

"The more carbs and sugars you eat, the more your appetite-control
cells are damaged, and potentially you consume more," Dr Andrews said.

Dr Andrews said the attack on appetite suppressing cells creates a
cellular imbalance between our need to eat and the message to the brain
to stop eating.

"People in the age group of 25 to 50 are most at risk. The neurons
that tell people in the crucial age range not to over-eat are being
killed-off.

"When the stomach is empty, it triggers the ghrelin hormone that
notifies the brain that we are hungry. When we are full, a set of
neurons known as POMC's kick in.

"However, free radicals created naturally in the body attack the
POMC neurons. This process causes the neurons to degenerate overtime,
affecting our judgement as to when our hunger is satisfied," Dr Andrews
said.

...

"A diet rich in carbohydrate and sugar that has become more and more
prevalent in modern societies over the last 20-30 years has placed so
much strain on our bodies that it's leading to premature cell
deterioration," Dr Andrews said.

12 November 2008

Doug McGuff, MD has an interesting new article, Fountain of Youth posted on his Ultimate Exercise site.

On May
23, 2007 a major stride in the quest for life extension occurred.
Researchers Simon Melov et al announced a treatment that successfully
reversed aging. (www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000465).
This reversal occurred not in worms, fish, or rats; but actually
occurred in human subjects. More importantly, this reversal was not
simply a marker of aging, but an actual reversal toward normal youthful
function at the genetic level. The researchers tested 596 genes that
appeared to be markers of declining function as a result of age. Most
of these genes were associated with mitochondrial function. This is
important for two reasons. First, the mitochondria are the powerhouses
for the cells of your body, they are the engine that makes us run.
Secondly, mitochondrial DNA is easier to study with greater certainty
of accuracy because all of your mitochondrial DNA comes only from your
mother. As a consequence, differences in expression cannot be
accounted for by the contribution of another person’s (i.e.-father’s)
DNA that may react differently under experimental conditions. The
study definitively identified 179 genes that were reversed by the
intervention, and as the study stated “the transcriptional signature
of aging was markedly reversed back to that of younger levels for most
genes that were affected by both age and exercise”.
what was this miracle treatment? The answer is STRENGTH TRAINING.
Strength training performed twice a week for a period of 26 weeks.
Even more amazing is that by standards of most people who participate
in training facilities such as Ultimate Exercise, it was strength
training that was done relatively poorly on substandard equipment. The
researchers had subjects perform leg press, chest press, leg extension,
leg flexion, shoulder press, lat pull-down, calf raise, abdominal
crunch and back extension for 3 sets of 10 reps, and arm flexion and
arm extension for 1 set of 10 reps. The equipment was Universal Gym,
Inc. equipment. Resistance was based on 50% of a 1 rep max and
progressed to 80% of a 1 rep max. Over the study period the subjects
increased their strength by 50% which made them only 38% weaker than 25
year old cohorts.

Further down in the article Doug connects these ideas with Arthur Devany's:

A New Definition of Aging

What is interesting about this landmark article is the genes that were
identified to be related to aging were genes that were largely involved
in synthesizing enzymes of anaerobic metabolism or transporting
anaerobic substrate for aerobic use. What therefore appears to be a
marker of youth, and consequently what gets lost with aging, is the
ability to perform high-intensity anaerobic work. This fits well with
a concept proposed by Dr. Arthur Devany (www.arthurdevany.com)
. Dr. Devany is an economist who developed the concept of Evolutionary
Fitness. While I differ in specific details of his exercise
recommendation, I believe his notions regarding diet, exercise and how
they effect the expression of genes handed down to us by evolution are
absolutely brilliant. The concept that Dr. Devany coined is Physiologic Headroom.
Physiologic headroom is basically described as “the difference between
the most you can do and the least you can do”. Dr. Devany notes that
when the difference between the most you can do and the least you can
do becomes zero, you are dead. Consequently, it is easy to extrapolate
that the process whereby the most you can do and the least you can do
decreases could be called aging. What determines the most you can do
is basically aneaerobic metabolism. Anaerobic metabolism precedes
aerobic metabolism and can cycle much more quickly. This makes sense
from an evolutionary standpoint because anaerobic metabolism is much
more primitive than aerobic metabolism which was a much later
evolutionary development. It therefore makes sense that aerobic
metabolism requires substrate from the anaerobic metabolism to run.
Once the ability to deliver that substrate declines, aerobic metabolism
must decline as well, and the amount of output that can be generated
from any kind of exercise will approach zero.

Doug ties a lot of this to HIT and SuperSlow training and I give him tremendous credit as perhaps its most articulate and thoughtful proponent. A bit further in the article he continues with:

If we embrace this concept of aging (the gap between maximal and minimal
output), and the type of training that enhances this capability; then
we must acknowledge that there is a type of exercise which can produce
the opposite result. Low intensity, steady state exercise will
actually accelerate aging by this definition. When exercise is of low
intensity, the slow and intermediate fibers are called upon at a rate
that does not result in fatigue and does not stimulate rapid cycling of
anaerobic metabolic pathways. As a result, anaerobic enzymes
down-regulate and fast twitch fibers are never called upon. An
adaptive response then occurs whereby the fast twitch fibers are
allowed to atrophy and die. This is because, if they are never used in
the face of this activity, they are simply dead weight which must be
carried along. While one may argue that this is an adaptation, we must
remember that not all adaptations are beneficial. In the process of
losing our fast twitch fibers, we do not just lose physiologic
headroom. We begin to lose the largest glucose sink in our body.
Glucose is stored as glycogen (long chains of glucose strung together
like a tinker-toy model). About 70 grams of glycogen can be stored in
the liver and 220 grams can be stored in the skeletal muscle. The
glycogen in the liver is used mainly to maintain a stable blood glucose
level. The glycogen stored in the muscle is used as emergency on-site
fuel for bursts of high intensity muscular work. The majority of the
glucose stored in muscle is in the fast-twitch fibers, because that is
where the fuel is needed for emergency anaerobic metabolism. When we
jettison these fast-twitch fibers, we set up a scenario for a rapid
decline in metabolic health. By losing the largest storage warehouse
for glucose in our body, we begin to lose insulin sensitivity. We
already only have a storage capacity of 290 grams at baseline (which is
way less carbohydrate than the average American consumes in a given
day). As we lose the glucose storing capability of these fast-twitch
fibers, we have nowhere for our dietary glucose to be stored and
glucose stacks up in the bloodstream. The liver and muscles become
completely full and decrease the number and sensitivity of their
insulin receptors to protect themselves from excess glucose being
transported into the cell (excess glucose binds to metabolic proteins
and enzymes in a process called glycosylation—imagine pouring pancake
syrup on your keyboard). Glucose then begins to stack up in the blood
which in turn stimulates the pancreas to make more insulin. This
creates a stimulus for continued decreases in muscle insulin
sensitivity. The body tries to protect itself by increasing
insulin sensitivity in other areas, most notably your fat cells. A
circuitous metabolic process then occurs where excess glucose is
circulated to the liver where it is converted to Triacylglycerol
(triglycerides) and is circulated to the fat cells for assembly and
storage. The relative increase in glucose metabolism through aerobic
pathways produces oxidative free radicals that produce inflammation and
accelerate the aging process. The details of all of this downstream
metabolic mayhem will be the subject of future articles and are
discussed in further detail (with supporting literature) in Body by Science.
Interestingly, if you ever get yourself into this predicament and visit
your doctor, you will be told to eat a high carbohydrate/low fat diet
and to take up steady state activity. If you are lucky, you may get
started on meds that kill your testosterone production and produce
weakness in what little muscle you still have left. What will really
turn around this metabolic process is high intensity strength training
combined with a diet based on evolutionary principles.

Another vote for strength training + paleo, and a warning about statins that "...kill your testosterone production...". Well worth the read.

07 November 2008

I met J... in Toronto she told me that you were very informed about nutritional supplements etc. I thought I would ask your advice and find out what you would suggest. I travel a lot and had a few accidents (car, falling off horses) and have started to develop osteoarthritis in my neck. I also start to get very stiff when I sit still for a long time, like on long distance flights. It helps when I can do regular exercise at home, yoga and working on my land which is physically hard work, for example cutting fire wood which I am doing right now) but when I am in some got forsaken place to work and can not wonder the streets easily (no time or for security reasons) I am usually taking major meds like ibuproven I wonder if you have any other suggestions, perhaps in terms of herbal supplements on what
else I can do.
Thanks and hope to hear from you soon, S

I found this funny, because my wife (fully encouraged by our devious children) takes endless pleasure in making fun of all the things I do to take care of myself. All the crueler because the luck of her genetics makes keeping fit and healthy a breeze. Ah well...

My response to S summarized a lot of my thoughts so I thought to post it here:

S.....,

Ha! I know the feeling. As I get older, I feel fine, except my parts keep going. Jane may have overstated my expertise, but I can suggest things that seem to work for me. First take a look at my blog www.AthleteAtAge.com. I try to keep it up to date on my latest thinking and sources, although events in the financial world and the elections have distracted me.

Aging (at least the bad things that come with it) appears to arise from several processes in the body. These include:

Dehydration,

Oxidation,

Calcification,

Inflammation (arthritis), and

One other that I can't remember right now.

Diet, exercise, supplements, and in some cases drugs can moderate all of these. Some think that problems in one area can amplify others.

Food quantity - look at "The Zone diet" it provides a baseline for determining quantity and proportion of macro nutrients (protein, fat, and carbohydrates) relative to your lean body mass.

Intermittent fasting - for periods between 12 and 16 hours per day (including sleeping hours) can have a very beneficial affect on metabolism, inflammation, insulin regulation (which aggravates inflammation). This appears to have the same affect as restricted calorie diets relative to life extension and retaining quality of life as we age. You need to consume the same number of calories as you otherwise would (or zone diet "blocks" if you go that way), just do it in the shorter feeding window. Drink lots of water even while you fast.

Any one of these will help, together they can provide remarkable affects in inflammation, hormone regulation, body composition, physical performance, and well being. Also note, almost all spices have anti-oxidant, anti-inflammatory, and insulin regulatory properties. If you drink coffee, stop.

Supplements:

fish oil - good for everything, TAKE LOTS! Much better than taking ibuprofen (which can throw off insulin regulation).

cinnamon - put it on everything you can. It regulates insulin and helps inflammation.

glucosamine & chondroitin with MSM - important for your joints. You need to take this on an empty stomach.

anti-oxidants: green tea, turmeric, resveratrol,

buffered vitamin C before bed offsets cortisol,

vitamin D3 (lots, you probably don't get enough exposure to the sun up north)

Water - drink lots 2 to 4 liters per day, great for everything but in your case it especially helps synovial fluid generation to lubricate joints.

I do joint mobility exercise before physical activity to wash the joints with synovial fluid, this lubricates them and prepares them for whatever else you do. Scott Sonnon has developed a lot of this work:

Intu-flow (joint mobility exercises) https://agelessmobility.3dcartstores.com/Intu-Flow_p_0-8.html get the video, you can do these anywhere.

Good YouTube video of Scott at http://www.youtube.com/watch?v=G6uK76TQYig&eurl=http://www.rmaxinternational.com/home/

Add short, intense, weight bearing exercise and you've got most of what you need to do to keep moving (for a long long time).

Finally for acute pain and inflamation I use DMSO topically. Use only 99.9% pure DMSO in water. Don't use any DMSO with aloe or anything else in it. No gels. Wash the area (your neck) with soap and water, wipe it with alcohol, then apply DMSO. It smells terrible, the smell lingers, it can give you a yucky garlic taste in your mouth, but it does remarkable things for inflammation from arthritis and injuries.

Good luck. Feel free to ask any other questions or request clarifications.